Chinnasamy Dhanalakshmi, Tector Matt, Chinnasamy Nachimuthu, Dennert Kate, Kozinski Karen M, Oaks Martin K
Immunotherapy Program, Aurora St. Luke's Medical Center, Aurora Health Care, Milwaukee, WI 53215, USA.
Cancer Immunol Immunother. 2006 Dec;55(12):1504-14. doi: 10.1007/s00262-006-0153-7. Epub 2006 Apr 13.
Fusion proteins consisting of the ligand-binding domain of CTLA4 covalently attached to an antigen (Ag) are potent immunogens. This fusion strategy effectively induces Ag-specific immunity both when introduced as a DNA-based vaccine and as a recombinant protein. CTLA4 is a ligand for B7 molecules expressed on the surface of antigen-presenting cells (APCs), and this interaction is critical for the fusion protein to stimulate Ag-specific immunity. We show that interaction of the fusion protein with either B7-1 or B7-2 is sufficient to stimulate immune activity, and that T cells are essential for the development of IgG responses. In addition, we demonstrate that human dendritic cells (DCs) pulsed with CTLA4-Ag fusion proteins can efficiently present Ag to T cells and induce an Ag-specific immune response in vitro. These studies provide further mechanistic understanding of the process by which CTLA4-Ag fusion proteins stimulate the immune system, and represent an efficient means of generating Ag-specific T cells for immunotherapy.
由与抗原（Ag）共价连接的CTLA4配体结合域组成的融合蛋白是有效的免疫原。当作为基于DNA的疫苗和重组蛋白引入时，这种融合策略可有效诱导Ag特异性免疫。CTLA4是抗原呈递细胞（APC）表面表达的B7分子的配体，这种相互作用对于融合蛋白刺激Ag特异性免疫至关重要。我们表明，融合蛋白与B7-1或B7-2的相互作用足以刺激免疫活性，并且T细胞对于IgG反应的发展至关重要。此外，我们证明用CTLA4-Ag融合蛋白脉冲处理的人树突状细胞（DC）可以有效地将Ag呈递给T细胞并在体外诱导Ag特异性免疫反应。这些研究为CTLA4-Ag融合蛋白刺激免疫系统的过程提供了进一步的机制理解，并代表了一种产生用于免疫治疗的Ag特异性T细胞的有效方法。
